With the advent of point of care testing in hospital emergency departments, it has become increasingly important to develop diagnostic products which are simple, rapid and convenient for the user to perform. This need has arisen because health care workers in an emergency department need results rapidly with a minimum of time given to the performance of a diagnostic test. Providing a diagnostic result in minutes allows a physician to treat a patient as soon as possible.
Point of care diagnostic tests frequently are performed on biological samples, such as whole blood or urine. Cells and particulate matter in biological samples can interfere with fluid flow in a test device, and thus impair the measurement of analytes in the biological fluid.
For example, in blood, red blood cells can interfere with spectroscopic measurements, and as the hematocrit varies, the volume of plasma in a given volume of blood varies. To overcome these problems, red blood cells are separated from plasma to allow for a more defined and uniform sample.
As a further example, urine can contain lymphocytes that can affect spectroscopic measurements, and flow through filters and capillaries. Thus, a device to filter out cells, particulate matter, or debris from a biological sample can improve the quality of an analytical procedure performed on the sample.
To achieve removal of particulates, incorporation of a filter into an assay device has been described in the prior art. For example, U.S. Pat. Nos. 4,477,575; 4,753,776; 4,987,085; and 5,135,719 refer to blood filter devices whereby a transverse flow of blood through a filter results in the separation of red blood cells from plasma. Sealing of the filter in the device to achieve effective filtration, and not allow sample to bypass the filter, has been a problem in the prior art. A small capillary or gap between the filter and the filter chamber walls often existed due to poor initial sealing, or because the gap formed with time. As a consequence, particulates in a fluid sample travel in the capillary space or gap rather than through the filter. Particulate matter which travels around the filter decreases the filtration efficiency, repeatability, and may cause the filter to be unacceptable for certain applications. Techniques, such as using glues, tapes and the like have been used to seal a filter into the filter chamber of such devices. The use of these materials to affect sealing has produced variable, and often poor sealing. Additionally, these sealing methods resulted in absorption of variable amounts of the sealing compound into the filter.
Another drawback of prior art filter devices is consequent to use of a relatively short transverse fluid flow path through a filter. The transverse flow path in a conventionally shaped filter (a filter with a length, width and substantially thinner depth) is the distance between the top and the bottom of the filter, the filter depth commonly referred to as the filter thickness Filters are generally 0.1 mm to 6 mm thick, this relatively short flow path produces relatively poor separation efficiency. A longer flow path would allow more particulates to be removed from fluid, thus, increasing the separation efficiency. U.S. Pat. Nos. 4,678,757; 5,135,719; 5,262,067 and 5,435,970, comprise filters treated with materials such as carbohydrates, agglutins and lectins, to affect separation of red blood cells from plasma. However, due to the relatively short fluid flow path, the filtration efficiencies in these teachings are not optimal. European Appl. No. 89300416.8, describes methods and devices which bind red blood cells to treated polycationic filters. However, treatment of filters introduces an additional process in device fabrication. A filter-device design that does not require treatment would be advantageous since the filter would be too costly and device manufacture would be less complicated; less complicated device designs are easier and more cost-effective to manufacture.
Embodiments with longer transverse flow paths have also been disadvantageous, however. U.S. Pat. No. 5,139,685 (“the '685 patent”), describes a cylinder of stacked filters, so that the device has a relatively long flow path. Although the '685 patent has a relatively long transverse fluid flow path pursuant to stacking of discrete filters, applications of this technique are limited. Namely, in the '685 patent, discrete filters are stacked and are under an applied pressure to achieve an efficient filtration of red blood cells from plasma. The pressurization of the filters is necessary to achieve a fast and efficient separation of particulate matter from the sample.
The relatively large amount of space required and the configuration of a design of the '685 patent does not lend itself to a convenient point of care diagnostic testing. Point of care diagnostic testing is facilitated by smaller and more convenient designs that can be easily manipulated by a health care worker, designs which are capable of being fed into hand-held instruments that provide quantitation of assay results. Devices capable of being fed into hand-held instruments (such as a reader) should be small and flat, and have smooth surfaces. Preferably a point of care device would not require an externally applied pressure.
Thus, there is a need for an efficient, compact, cost-effective filtration device. There is also a need for a means to effectively seal a filter within a device, whereby the fluid flow path is optimized, leading to increased filtration efficiency. Most desirably, there is a need for a sealing means that makes device fabrication tolerances less crucial and device manufacture more economical.